Topical mecamylamine for diabetic macular edema.

PubMed ID: 20189159

Author(s): Campochiaro PA, Shah SM, Hafiz G, Heier JS, Lit ES, Zimmer-Galler I, Channa R, Nguyen QD, Syed B, Do DV, Lu L, Monk J, Cooke JP, Kengatharan MK, Hsu HH. Topical mecamylamine for diabetic macular edema. Am J Ophthalmol. 2010 May;149(5):839-51.e1. doi: 10.1016/j.ajo.2009.12.005. Epub 2010 Feb 26. PMID 20189159

Journal: American Journal Of Ophthalmology, Volume 149, Issue 5, May 2010

PURPOSE Stimulation of nicotinic acetylcholine (nACh) receptors on vascular endothelial cells promotes angiogenesis and vascular permeability in animal models. The safety and bioactivity of topical mecamylamine, an antagonist of nACh receptors, was tested in patients with diabetic macular edema.

DESIGN A multicenter phase I/II clinical trial.

METHODS Twenty-three patients with chronic diabetic macular edema received 1% mecamylamine topically twice daily for 12 weeks, the primary end point. Patients underwent safety assessments, measurement of best-corrected visual acuity (BCVA), and measurement of foveal thickness using optical coherence tomography at baseline, 1, 4, 8, 12, and 16 weeks.

RESULTS Mecamylamine drops were well tolerated and there were no drug-related safety problems. Mean improvement in BCVA at 1, 4, 8, 12, and 16 weeks was 2.8, 1.9, 2.4, 0.8, and 3.1 letters, respectively. There was little change in mean excess foveal thickness. There was substantial heterogeneity in response, because 8 patients showed convincing improvement in BCVA, foveal thickness, or both, 9 patients showed equivocal or no substantial changes, and 4 patients showed worsening. Five patients showed a substantial improvement in BCVA, foveal thickness, or both between their last visit while receiving mecamylamine and 1 month after stopping mecamylamine.

CONCLUSIONS This study suggested that administration of topical mecamylamine, a nonspecific nACh receptor blocker, may have heterogeneous effects in patients with diabetic macular edema. Variable expression of nACh receptor subtypes on endothelial cells that have different effects on permeability would provide an explanation for these results and should be investigated, because more specific nACh receptor blockers may dissociate antipermeability and propermeability effects.

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